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Tumor Biology

, Volume 36, Issue 10, pp 7557–7568 | Cite as

Orthotopic inflammation-related pancreatic carcinogenesis in a wild-type mouse induced by combined application of caerulein and dimethylbenzanthracene

  • Chen Liang
  • Zhen Wang
  • Li Wu
  • Chen Wang
  • Bao-Hua Yu
  • Xiu-Zhong Yao
  • Xiao-Lin Wang
  • Ying-Yi Li
Research Article

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies, with a poor long-term prognosis, and effective therapeutic options are lacking. Observing the dynamics of the pathogenesis of pancreatic intraepithelial neoplasia (PanIN) and PDAC in tumor models can facilitate understanding of the molecular mechanisms involved in early PDAC. Furthermore, it can compensate for the research limitations associated with analyzing clinical specimens of late-stage PDAC. In this study, we orthotopically treated the pancreas with dimethylbenzanthracene (DMBA) combined with caerulein in wild-type C57BL/6 J mice to induce inflammation-related pancreatic carcinogenesis. We observed that DMBA and caerulein treatment induced a chronic consumptive disease, which caused a decrease in the relative body and pancreas weights, diminishing the health status of the mice and enhancing the inflammation-related histological changes. Moreover, mid-dose and high-frequency treatment with caerulein caused prolonged inflammatory damage to the pancreas and contributed to a permissive environment for the development of PDAC. CXCL12/CXCR4, CCL2/CCR2, and several cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were upregulated in the tumor tissue of DMBA and caerulein-induced PDAC mice. This orthotopic mouse pancreatic carcinogenesis model mimic human disease because it reproduces a spectrum of pathological changes observed in human PDAC, ranging from inflammatory lesions to pancreatic intraepithelial neoplasia. Thus, this mouse model may improve the understanding of molecular mechanisms underlying the injury-inflammation-cancer pathway in the early stages of pancreatic carcinogenesis.

Keywords

DMBA Caerulein Pancreatitis Pancreatic cancer 

Notes

Acknowledgments

This work was supported in part by the National Science Foundation of China (NSFC) (30973476, 81272727, and 81472223), and the Shanghai Committee of Science and Technology (12DZ2260100).

The authors would like to thank Dr. H.Y. Gu, P. Zhang, Y.H. Xin, and Y. Cao of the Cancer Research Institute, Fudan University Shanghai Cancer Center and C.-X. Fu of the Siemens Shenzhen Magnetic Resonance Ltd., Siemens MRI Center for their technical support.

Open access

This article is distributed under the terms of the Creative Commons Attribution License, which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Chen Liang
    • 1
    • 2
  • Zhen Wang
    • 1
    • 2
  • Li Wu
    • 3
  • Chen Wang
    • 1
    • 2
  • Bao-Hua Yu
    • 2
    • 4
  • Xiu-Zhong Yao
    • 3
  • Xiao-Lin Wang
    • 3
  • Ying-Yi Li
    • 1
    • 2
  1. 1.Cancer Research InstituteFudan University Shanghai Cancer CenterShanghaiChina
  2. 2.Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina
  3. 3.Department of ImageFudan University Shanghai Zhongshan Hospital, Shanghai Medical CollegeShanghaiChina
  4. 4.Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina

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